Autism spectrum disorders (ASDs) are a group of heterogenous neurodevelopmental disorders affecting 1 in 59 children. Syndromic ASDs are commonly associated with chromosomal rearrangements or dosage imbalance involving a single gene. Many of these genes are dosage-sensitive and regulate transcription, protein homeostasis, and synaptic function in the brain. Despite vastly different molecular perturbations, syndromic ASDs share core symptoms including social dysfunction and repetitive behavior. However, each ASD subtype has a unique pathogenic mechanism and combination of comorbidities that require individual attention. We have learned a great deal about how these dosage-sensitive genes control brain development and behaviors from genetically-engineered mice. Here we describe the clinical features of eight monogenic neurodevelopmental disorders caused by dosage imbalance of four genes, as well as recent advances in using genetic mouse models to understand their pathogenic mechanisms and develop intervention strategies. We propose that applying newly developed quantitative molecular and neuroscience technologies will advance our understanding of the unique neurobiology of each disorder and enable the development of personalized therapy.

自闭症谱系障碍（ASD）是一组异质性神经发育障碍，影响59名儿童中的1名。症状性ASD通常与涉及单个基因的染色体重排或剂量失衡有关。这些基因中的许多对剂量敏感，并调节大脑中的转录，蛋白质稳态和突触功能。尽管分子扰动大不相同，但综合症ASD仍具有核心症状，包括社交功能障碍和重复行为。但是，每种ASD亚型都有其独特的致病机制和合并症的组合，需要个人注意。我们已经从基因工程小鼠那里学到了很多有关这些剂量敏感基因如何控制大脑发育和行为的知识。在这里，我们描述了由四个基因的剂量失衡引起的八种单基因神经发育障碍的临床特征，以及使用遗传小鼠模型了解其致病机制和制定干预策略的最新进展。我们建议应用最新开发的定量分子和神经科学技术将增进我们对每种疾病独特的神经生物学的了解，并能够发展个性化疗法。